| Partâ… Significance of serum ghrelin level in differentpeople with atherosclerosisBackground Many different biological effects could be found following the binding ofghrelin with its receptor.The receptor mRNA of ghrelin is widely distributed incardiovascular tissue.From the foregone documents of ghrelin,we found that ghrelin act tosafeguard the function of cardiovascular tissue via inhibiting inflammation,anti-apoptotic,regulating lipid metabolism and so on.However,the exactly serum level of ghrelin indifferent people with atherosclerosis have not been clarified,and whether a correlation existbetween the different concentration of ghrelin and CAD or DM etc.is still unknown.Objective Investigating the serum level of ghrelin in different people and observing therelationship between the variation of ghrelin and diseases.Methods and results A comparative study was performed in patients with different age,obesity,coronary artery disease (CAD) and diabetes mellitus (DM).Enzyme linkedimmunosorbent assay was used to detect plasma levels of ghrelin,at the same time,generally selected biochemical parameters such as total cholesterol (TC),triglyceride (TG),high density lipoprotein cholesterol (HDLc),etc.were detected with submitted blood,collecting clinical data,analyzing the general clinical feature:age,sex,smoking,body massindex (BMI),hypertension and so on.We found that,compared with young people,serumlevel of ghrelin in older age-group reduced from (2.51±0.77)ng/ml to (1.43±0.64)ng/ml, p=0.009.Compared with middle-aged people (2.240.32)ng/ml,p=0.036,showedstatistically significant differences.The serum level of ghrelin decreased significantly withage.Further analysis indicated the positive linear correlation between ghrelin level and age,rp=-0.564,p=0.015.Compared with control group,serum level of ghrelin in obesity people(BMI≧28Kg/m2) reduced from (2.77±1.49)ng/ml to (1.87±0.89)ng/ml,and there aresignificant difference,p=0.047.After correction of age,serum level of ghrelin in CADpeople reduced from (3.00±0.29)ng/ml to (1.82±0.34)ng/ml,p=0.025,the differencebetween them was significant in statistics.Compared with control group,serum level ofghrelin in DM people reduced from (3.35±13.02)ng/ml to (2.41±0.74)ng/ml,and thedifference is significant,p=0.013.Conclusions Peripheral blood serum level of ghrelin show a tendency of decline with age.Serum level of ghrelin in people with obesity,CAD and DM would lead to further decrease.The data provide the natural phenomenon of ghrelin,which may be the basis of furtherstudy about the function of ghrelin.Partâ…¡The progression of atherosclerosis could be retarded byghrelin via inhibiting the proinflammatory function of Th17 cellsBackground Recently,Th17 cell has been described as one neotype CD4+ T cell,which could produce interleukin-17 (IL-17) especially and serve as the important regulatorsof inflammatory diseases.IL-17 could promote the secretion of TNF-α,IL-6 frommononuclear macrophages;and by combining these two inflammatory factors,IL-17 couldenhance the inflammatory reaction.It's well known that atherosclerosis is a chronicinflammatory disease,IL-17,TNF-αand IL-6,which close related with atherosclerosis,play an important role in the onset of Anorexia-Cachexia Syndrome.However,what is therelationship between ghrelin,the important appetite regulation hormone,and theinflammatory factors described above? Whether the protective effect of ghrelin on the progress of atherosclerosis is concerned with these inflammatory factors? Few documentshave described it.Objective To investigating the serum level of ghrelin and Th17 cells content and toobserve the changing of the inflammatory factors described above in the PBMCs afterbeing interfered by ghrelin.Study the mechanism of Ghrelin on retarding the developmentof atherosclerosis.Methods The objectives were divided into two groups after detecting the intima-mediathickness (IMT),i.e.atherosclerosis (AS) group,including 37 patients (IMT≧1.2mm)and control group,including 31 patients (IMT＜1.2mm).Flow cytometry was used to detectthe percentage of Th17 in CD4+T cells;Plasma concentrations of Ghrelin and Th17-relatedcytokines (IL-17,IL-6,TNF-α) were measured by enzyme-linked immunosorbentassay(ELISA).Peripheral blood mononuclear cells (PBMCs) of patients with AS werecultured in vitro,and the concentration of inflammation factors,above-mentioned,weredetected after being interfered by Ghrelin.Results The percentage of Th17/CD4+ T was found to be significantly higher in AS group[(1.92±0.52)%] than that in control group [(0.59±0.32)%](P＜0.05).The concentration ofGhrelin markedly decreased in AS group [(2.19±0.84)ng/ml] (P＜0.05);and Th17-relatedcytokines (IL-17,IL-6,TNF-α) markedly increased in AS group [(101.29±25.00)pg/ml,(7.67±3.58)pg/ml,(17.98±3.16)pg/ml] compared with control group [(76.97±27.64)pg/ml,(3.89±3.50)pg/ml,(6.38±1.27)pg/ml] (P＜0.05);Ghrelin could inhibit the expression of thecytokines,and this inhibiting effect was in a dose-dependent manner (P＜0.05).Therelationship between Ghrelin and IMT,cytokines were negative.The correlation coefficientbetween Ghrelin and IMT,IL-17,IL-6 TNF-αwere r=-0.498,-0.544,-0.363 and -0.565,respectively (P＜0.05).Conclusion Ghrelin retards the development of AS via inhibiting the expression ofTh17-related cytokines. Partâ…¢Effects of Ghrelin on the Expression ofAcyl Coenzyme A:Cholesterol Acyltransferases-1 during Foam Cells FormationBackground Acyl-CoA:cholesterol acyltransferases (ACAT-1) could catalysis freecholesterol into cholesterol ester,and then form the foam cells.The foam cells formationwould be inhibited via down-regulating the expression of ACAT1.As we all know,ghrelincould inhibit the formation of foam cells via promoting the efflux of free cholesterol fromfoam cells by up-regulating the expression of ATP-binding cassette transporter A1.Therefore,if ghrelin has both functions about up-regulating ABCA1 and down-regulatingACAT1,the formation of foam cells would be inhibited.The further mechanism of ghrelinanti-atherosclerosis would be clarified.The data in this field has not been reported.Objective To investigate the effects of ghrelin on the expression of ACAT-1 and thecholesterol content of foam cells during the formation of foam cells.Methods The human monocytic leukemia cell line (THP-1) was chosen in our study.Thedifferentiation of THP-1 cells into macrophages was induced by phorbol 12-myristate13-acetate (PMA).Macrophages were incubated with oxidized LDL (Ox-LDL) to generatefoam cells.The cells were divided into four groups to carry out control study:control group(Ox-LDL),different concentration group of ghrelin (10-5,10-6,10-7 mol/L).Ghrelin ofdifferent concentrations were treated for 2 hours before Ox-LDL(100mg/L) were added in.After being incubated for 24 hours,the cells medium were changed,and then apoA-â… (10mg/L) were added in with 0.3%BSA.After 12 hours incubation,the cells were collectedfor detection.The effect of variance of cholesterol content was measured by zymochemistryvia-fluorospectrophotometer,the lipid droplet content were observed by Oil red stainingmethod,the ACAT-1 protein and mRNA levels were detected by Western blotting andRT-PCR.Results Ghrelin could reduce the formation of lipid droplet of foam cells derived fromTHP-1 macrophages;Ghrelin reduced the content of cholesterol ester in foam cellsobviously,the cholesterol ester content of foam cells decreased (14.6±0.5)%,(28.3±1.5)%and (45.4±1.0)%,separately with increasing concentration of ghrelin.Further analysisindicated the positive linear correlation between the protein and mRNA expression of ACAT1 and cholesterol content,r=0.942,0.935,separately.ACAT-1 protein and mRNAlevels were also decreased.Ghrelin could reduce ACAT-1 protein mass and mRNA level ina dose-dependent manner.Not change was observed about the amount of lipid dropletstained by Oil Red O as time prolonging.The changing about the expression of ACAT1 wasnot significant,p＞0.05.Conclusion Ghrelin might retard the formation of atherosclerosis via down-regulating theexpression of ACAT-1.The inhibiting effect of ghrelin on the expression of ACAT1 was ina dose-dependent,not a time-dependent manner.
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